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ID: ALA1147465

Journal: Bioorg Med Chem Lett

Title: Nucleic acid-binding ligands identify new mechanisms to inhibit telomerase.

Authors: Dominick PK, Keppler BR, Legassie JD, Moon IK, Jarstfer MB.

Abstract: We screened a small library of known nucleic acid-binding ligands in order to identify novel inhibitors of recombinant human telomerase. Inhibitory compounds were classified into two groups: Group I inhibitors had a notably greater effect when added prior to telomerase assemblage and Group II inhibitors displayed comparable inhibition when added before or after telomerase assemblage. Hoechst 33258, a Group I inhibitor, was found to interact tightly (KD = 0.36 microM) with human telomerase RNA (hTR) leading us to propose that hTR is the molecular target for this and other Group I inhibitors. Our results suggest that hTR can be exploited as a small-molecule drug target and provide several new structural motifs for the further development of novel telomerase inhibitors.

CiteXplore: 15177454

DOI: 10.1016/j.bmcl.2004.04.055